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E J Thomas

Publications and source records attributed to E J Thomas.

At least 19 recordsLinked to original sources
PubMed1998

Absorptive apical amiloride-sensitive Na+ conductance in human endometrial epithelium.

1. Human endometrial epithelial cells cultured on porous tissue culture supports formed tight, polarized epithelial monolayers with features characteristic of tight epithelia. Endometrial epithelial layers generated significant transepithelial electrical resistance (750 Omega cm2) and potential difference (15.3 mV), with an inward short-circuit current (Isc; 20.5 microA cm-2). 2. The Isc was linearly proportional to the external Na+ concentration and was abolished in the absence of Na+. The Isc was sensitive to apical amiloride. Net 22Na+ flux was in the absorptive apical to basolateral direction and fully accounted for the inward Isc. In addition, apical to basolateral and net 22Na+ transport were reduced in the presence of amiloride. 3. The Isc was also sensitive to addition of ouabain and Ba2+ to the basal solution, consistent with a role for basolateral Na+-K+-ATPase and K+ channels in generation of the current. 4. These data demonstrate that human endometrial epithelial cells in primary culture produce tight, functional monolayers on permeable supports. We provide the first evidence that human endometrial epithelial cells have an inward Isc accounted for by an amiloride-sensitive Na+ conductance. The Na+-absorptive function of the endometrium may provide an appropriate environment for sperm function and embryo growth.

Absorption↗
PubMed1998

Mutation of galactose-1-phosphate uridyl transferase and its association with ovarian cancer and endometriosis.

Impaired galactose metabolism has been proposed as a risk factor for ovarian cancer and endometriosis, which is a putative precursor of endometrioid and clear cell histological sub-types of ovarian cancer. The prevalence of the most common galactose-I-phosphate uridyl transferase gene mutations, Q188R and N314D, was assessed in 206 women with ovarian cancer, 78 women with endometriosis and 248 controls. No Q188R mutations were found in any of the groups. A statistically significant increase in the frequency of N314D mutations was observed in women with serous and undifferentiated histological sub-types of ovarian cancer, but not mucinous, endometrioid or clear cell sub-types. There were no significant differences observed in the N314D mutation frequency between women with endometriosis (18%) and controls (17%). Our results support previous reports of an association of impaired galactose metabolism with serous and undifferentiated ovarian cancers but contradict previous findings of increased N314D mutation frequencies among women with endometriosis and endometrioid and clear cell sub-types ovarian cancer.

Adult↗
PubMed1998

Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors.

Epithelial ovarian cancer comprises three major histological subtypes (serous, mucinous, and endometrioid), and it is becoming clear that the developmental pathways for these subtypes are fundamentally different. In particular, endometrioid ovarian cancers probably arise by the malignant transformation of ectopic endometrial implants called endometriosis and not the ovarian surface epithelium. The PTEN/MMAC gene on chromosome 10q23 is a tumor suppressor implicated in the pathogenesis of a wide variety of malignancies, but to date, somatic mutations in PTEN have not been identified in studies of predominantly serous ovarian cancers. In endometrial cancers, PTEN mutations are very common in tumors of the endometrioid type but have rarely been found in serous types, and we hypothesized that a similar histological subtype bias might be occurring in ovarian cancer. We have analyzed 81 ovarian tumors, including 34 endometrioid, 29 serous, 10 mucinous, and 8 clear cell tumors, for loss of heterozygosity (LOH) on 10q23 and for mutations in all 9 coding exons of PTEN. LOH was common among the endometrioid (43%) and serous (28%) tumors but was infrequent among the other histological subtypes. Somatic PTEN mutations were detected in seven (21%) of the endometrioid tumors, and in all informative cases, the mutation was accompanied by loss of the wild-type allele. One mucinous tumor without 10q23 LOH was shown to harbor two somatic PTEN mutations. In this tumor, the histological appearance of the mucinous areas was atypical, and the mucinous areas contained foci of endometrioid differentiation. The majority of tumors with PTEN mutations were grade 1 and/or stage 1, suggesting that inactivation of PTEN is an early event in ovarian tumorigenesis. No PTEN mutations were found among the serous or clear cell tumors. The identification of frequent somatic PTEN mutations in endometrioid ovarian tumors indicates that it plays a significant role in the etiology of this subtype. The absence of mutations in other histological subtypes is consistent with the hypothesis that epithelial ovarian cancers arise through distinct developmental pathways.

Adenocarcinoma, Clear Cell↗
PubMed1998

Allelotyping of endometriosis with adjacent ovarian carcinoma reveals evidence of a common lineage.

Endometriosis is a common gynecological disease in which tissue similar to the endometrium proliferates at sites outside the uterine cavity. Malignant transformation of endometriosis to endometrioid and clear cell ovarian carcinomas has been documented in histological studies, but no molecular genetic evidence exists to support that endometriosis is the clonal precursor of such malignancies. We examined 14 cases of endometriosis synchronous with ovarian cancer for loss of heterozygosity on 12 chromosome arms, X chromosome inactivation, and TP53 mutation to determine whether they shared genetic alterations. In all four of the cases where the carcinoma had arisen within endometriosis and in five of the seven cases where the carcinoma was adjacent to the endometriosis, common genetic lesions were detected, consistent with a common lineage. A TP53 mutation was also detected in one case of endometriosis adjacent to carcinoma. These findings support the numerous histological observations that endometrioid and clear cell ovarian carcinomas may arise through malignant transformation of endometriotic lesions.

Adult↗
PubMed1998

Historical prospective cohort study of the recurrence of pain after discontinuation of treatment with danazol or a gonadotropin-releasing hormone agonist.

OBJECTIVE: To determine the duration of time to the recurrence of pain attributable to endometriosis after the discontinuation of treatment with danazol or a GnRH agonist (GnRH-a) in patients who have had a satisfactory response to the treatment. DESIGN: Retrospective study. SETTING: Nine academic medical centers in three countries. PATIENT(S): Three hundred twenty-seven women with diagnosed and staged endometriosis who were treated with at least 6 months of danazol or a GnRH-a and who experienced significant pain relief with therapy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Duration of pain relief after completion of treatment as determined by a patient-initiated report of pain recurrence or increase in pain severity requiring intervention. RESULT(S): The median time to the recurrence of pain was 6.1 months for patients treated with danazol and 5.2 months for patients treated with a GnRH-a. CONCLUSION(S): Although there was a lack of uniformity in treatment effects across sites, the analyses have taken into account major covariant effects. The time to the recurrence of endometriosis-associated pain after danazol treatment was slightly longer than that after GnRH-a treatment.

Adult↗
PubMed1998

Predictive value of creatine kinase (CK)-MB for diagnosis of acute myocardial infarction after major noncardiac surgery.

BACKGROUND: The aim of this study was to provide insight into the interpretation of CK-MB data after major noncardiac surgery. METHODS: Some 3,321 patients who underwent major non-emergent noncardiac procedures (orthopedic 31%, intrathoracic 12%, vascular 22%, other 35%) were studied. All patients had at least two CK samples measured postoperatively. RESULTS: Acute myocardial infarction was diagnosed in 43 (1.3%) patients using study criteria including CK-MB and electrocardiographic data. All of the various threshold values of peak CK-MB values and peak CK-MB as a percentage of total CK had poor positive predictive values because of high false positive rates and the low rate of acute myocardial infarction. CONCLUSION: These data demonstrate the need for markers of myocardial injury with greater cardiac specificity after noncardiac surgery.

Aged↗
PubMed1998

Endometriosis: a continuing enigma?

Endometriosis is a common gynaecological disease but remains a poorly understood condition. Fundamental questions about the aetiology, pathophysiology, diagnosis, natural history and treatment are still unanswered by the extensive research into endometriosis. This article will outline present understanding of endometriosis and the advances provided by recent research.

Endometriosis↗
PubMed1997

Body mass index as a correlate of postoperative complications and resource utilization.

PURPOSE: To describe the relationship of body mass index (BMI) with postoperative complications and resource utilization. PATIENTS AND METHODS: Two thousand nine hundred and sixty-four patients 50 years or older undergoing elective noncardiac surgery with an expected length of stay > or = 2 days were enrolled in a prospective cohort study to measure major cardiac complications, noncardiac complications, length of stay, and costs. The setting was an urban teaching hospital. A preoperative history, physical, electrocardiogram (ECG), and chart review were performed by study personnel. Postoperative complications were detected by ECGs, creatine kinase and creatine kinase MB levels, and daily chart review. Total costs were obtained from the hospital's computerized database. RESULTS: Complication rates were not different among BMI groups (underweight < 20, normal 20 to 29, overweight 30 to 34, most overweight > 34), but patients with BMI 30 to 34 and > 34 who underwent abdominal or gynecologic procedures had significantly higher wound infection rates (11% each) than normal weight patients (4.7%) or the underweight (0%). After adjusting for age, race, gender, smoking history, comorbid diseases, procedure type, and insurance status, there were nonsignificant trends toward increased resource utilization by the most overweight patients (BMI > 34). These patients stayed 0.8 days longer (P = 0.13) and had total costs that were $843 higher (P = 0.17) than patients of normal weight (BMI 20 to 29). The underweight patients stayed 0.9 days longer (P = 0.23) and had total costs that were $3,150 higher (P = 0.04) than patients of normal weight. Quadratic models to test for a U-shaped relationship found no correlation between BMI and length of stay, but did find that BMI was significantly correlated with total costs (P = 0.04). This relationship persisted when patients who had complications were excluded from the analysis. CONCLUSIONS: Overall, BMI was not significantly correlated with postoperative complications or length of stay. However, overweight patients who underwent abdominal or gynecologic procedures had higher wound infection rates, and patients with the highest and lowest BMIs had significantly higher adjusted total costs.

Age Distribution↗
PubMed1997

Prognostic value of cardiac troponin T after noncardiac surgery: 6-month follow-up data.

OBJECTIVES: We sought to evaluate the prognostic significance of cardiac troponin T (TnT) serum levels after noncardiac surgery. BACKGROUND: Cardiac TnT has been found to be marker for myocardial injury, but elevations of TnT are common in patients undergoing noncardiac surgery without clinical evidence of severe ischemia. METHODS: We studied 772 patients who underwent major noncardiac procedures and did not have major cardiovascular complications during their inpatient course. Total serum creatine kinase (CK) and cardiac TnT were measured according to a protocol that included sampling in the recovery room and during the next 2 days. A 6-month follow-up interview was performed for 722 (94%) of the patients. RESULTS: Elevated cardiac TnT and CK-MB results were detected for 92 (12%) and 211 (27%) patients, respectively. During the follow-up period, there were 19 (2.5%) major cardiac complications, including 14 cardiac deaths, 3 nonfatal myocardial infarctions and 2 admissions for unstable angina. Compared with patients with cardiac TnT values < 0.1 ng/ml, patients with elevated TnT had a relative risk for cardiac events of 5.4 (95% confidence interval: 2.2 to 13, p = 0.001), whereas CK-MB was not correlated with postdischarge cardiac events. In multivariate logistic regression analysis adjusting for preoperative clinical and CK-MB data, a cardiac TnT value > 0.1 ng/ml was in independent correlate of cardiac events (adjusted odds ratio 4.6, p < 0.05). This correlation was a function of the relation of elevated TnT levels with postoperative in-hospital congestive heart failure and new sustained arrhythmias, suggesting that elevated postoperative TnT levels detected myocardial ischemia during these clinical events. CONCLUSIONS: We conclude that an abnormal TnT level in patients undergoing noncardiac surgery may be a useful marker of ischemic disease and a predictor of 6-month prognosis.

Arrhythmias, Cardiac↗
PubMed1997

Gonadotrophin regulation of production of tissue inhibitor of metalloproteinases-1 by luteinized human granulosa cells: a potential mechanism for luteal rescue.

Human granulosa cells were maintained in culture with extracellular matrix in the presence or absence of human chorionic gonadotrophin (HCG) using a defined culture medium. Such cultures are maintained by gonadotrophin in a manner suggesting that features of 'luteal rescue' may be occurring in vitro. Western analysis of culture medium demonstrated that the granulosa cells produced tissue inhibitor of metalloproteinases (TIMP)-1 but not TIMP-2. The presence of TIMP-1 in cultured cells was also detected immunocytochemically. Immunoassay of TIMP-1 output revealed that HCG exposure for 7 days caused a 2-fold increase in TIMP-1 production versus control reaching maximum at approximately 1 ng HCG/ml. The sensitivity of this response to HCG was similar to that observed for stimulation of progesterone production. Delayed addition of HCG, from day 4 of culture, elicited increases in TIMP-1 which were evident within 24 hours, and were not explained by changes in cell replication or survival. Removal of HCG from cultures previously luteinized with HCG for 6 days resulted in a fall in TIMP-1 production. Thus TIMP-1 production by luteinized granulosa cells in culture is gonadotrophin dependent. We speculate that prolonged cellular function associated with 'luteal rescue' may result from increased extracellular matrix stability mediated by up-regulation of TIMP-1 production.

Cells, Cultured↗
PubMed1996

Microsatellite analysis of endometriosis reveals loss of heterozygosity at candidate ovarian tumor suppressor gene loci.

Endometriosis is a very common gynecological condition in which tissue similar to endometrium proliferates at sites outside the uterine cavity, most commonly the ovary. Although it generally remains a benign condition, malignant transformation has been documented. and it is commonly found in association with endometrioid subtype ovarian cancer. Tumor suppressor genes are commonly altered in ovarian cancers, and the development of endometriosis may involve mutations in the same class of genes. We have investigated this possibility by examining DNA from 40 cases of endometriosis for clonal status, alterations in TP53 and RASK, and allelic losses at candidate ovarian tumor suppressor loci on chromosome arms 6q, 9p, l1q, 17p, l7q, and 22q. The majority of endometriotic cysts were monoclonal, but interestingly, 8 of 10 normal endometrial glands were also monoclonal, demonstrating that both are able to develop from a single progenitor cell. No mutations were detected in TP53 or RASK. Loss of heterozygosity (LOH) was detected on chromosomes 9p (18%), 1lq (18%), and 22q (15%). In total, 11 of 40 (28%) cases demonstrated LOH at one or more of these loci. This study, which is the first to report LOH in endometriosis, supports the notion that tumor suppressor gene inactivation may play a role in the development of at least a subset of cases.

Base Sequence↗
PubMed1996

Troponin T as a marker for myocardial ischemia in patients undergoing major noncardiac surgery.

To assess the diagnostic performance of cardiac troponin T as a marker for myocardial injury in patients undergoing major noncardiac surgery, we prospectively collected preoperative and postoperative clinical data, including measurements for creatine kinase (CK), CK-MB, and troponin T for 1,175 patients undergoing major noncardiac surgery. Acute myocardial infarction was diagnosed in 17 patients (1.4%) by a reviewer who was blinded to troponin T data and who used CK-MB and electrocardiographic criteria to define acute myocardial infarction. Other predischarge major cardiac complications were detected for another 17 patients. Troponin T elevations (>0.1 ng/ml) occurred in 87% of patients with and in 16% of patients without myocardial infarction. Among patients without myocardial infarction, troponin T was elevated in 62% of patients with and in 15% of patients without major cardiac complications. Receiver-operating characteristic analysis indicated that troponin T had a performance for the diagnosis of acute myocardial infarction similar to CK-MB, and a significantly better correlation with other major cardiac complications in patients without definitive infarction. Future research should seek to determine the significance of troponin T elevations in patients without complications.

Aged↗
PubMed1996

Patient noncompliance with medical advice after the emergency department visit.

STUDY OBJECTIVE: To determine the correlates of compliance with follow-up appointments and prescription filling after an emergency department visit. METHODS: This prospective cohort study was undertaken as part of the Emergency Department Quality Study evaluation of five urban teaching hospital EDs in the northeastern United States. Of 2,757 eligible patients who presented with abdominal pain, asthma, chest pain, hand lacerations, head trauma, or first-trimester vaginal bleeding and were enrolled during 1-month period, 2,315 (84%) completed on-site baseline questionnaires. Information about diagnoses, socioeconomic status, discharge instructions, insurance status, and primary care was obtained from the on-site patient surveys and from reviews of medical records. A 76% random sample of patients who completed the questionnaire was generated, and 1,386 patients (79% of the sample) were interviewed by telephone approximately 10 days after their ED visit to determine compliance with follow-up appointments and prescription filling. RESULTS: Of the 1,386 patients interviewed at 10 days, 914 (66%) had been discharged from the ED, and 408 (45%) of those discharged recalled being advised to take a medication. Fifty of these patients (12%) reported that they did not obtain the medication. Significant independent correlates of not filling prescriptions were lack of insurance (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.1 to 5.5) and dissatisfaction with discharge instructions (OR, 2.8; 95% CI, 1.2 to 6.4). Two hundred thirty-five (26%) of the discharged patients said they were given follow-up appointments and did not have an appointment pending at the time of the interview; 77 (33%) of these patients reported having missed their appointment. The only significant independent correlate of missing follow-up appointments was being given a telephone number to call instead of leaving the ED with an appointment scheduled (OR, 3.8; 95% CI, 1.7 to 8.8). CONCLUSION: Not having an appointment made before leaving the ED was an independent correlate of missing follow-up appointments. Lack of insurance and dissatisfaction with discharge instructions were independent correlates of not filling prescriptions.

Adult↗
PubMed1996

Spouse enabling of alcohol abuse: conception, assessment, and modification.

This article presents a conception of spouse enabling of partner alcohol abuse, a review of its dysfunctions, and an approach to assessment and modification to reduce spouse enabling behavior. Based on experience with its use in unilateral family therapy with many spouses of treatment-refusing alcohol abusers, procedural guidelines, treatment methods, two case examples from a crossover experimental dyad, and clinical results for the two cases in the dyad are described. Also presented are practice issues, characteristics of spouse enabling as they relate to disenabling intervention, and areas of possible application of the disenabling program.

Adult↗
PubMed1996

Effect of human chorionic gonadotrophin on the detachment of human granulosa cells from extracellular matrix layered onto glass or plastic.

We have previously shown that human granulosa cells cultured on a thin layer of extracellular matrix (ECM) are lost from culture in the absence of gonadotrophin. We now examine the effect of plating ECM onto glass or plastic. Such a comparison revealed that loss of cells from control cultures was more rapid when ECM was on glass, whereas cultures maintained with human chorionic gonadotrophin (HCG) showed greater stability when ECM was on plastic. The dose range of HCG required for the effect on cell retention was similar to that required for stimulation of progesterone production. Electron microscopy of cells freshly released as clusters revealed that many cells appeared undamaged, and confocal microscopy of cells stained with propidium iodide showed an absence of fragmented nuclei. Taken together, this evidence suggests that apoptosis is not the cause of cell release. We conclude that cells are released from culture, not as a result of cell death, but via an active process suppressed by HCG.

Cell Adhesion↗
PubMed1996

The relevance of asymptomatic endometriosis.

Asymptomatic endometriosis is likely to be a physiological phenomenon of very limited relevance to both the physician and the patient. The evolution of our understanding of this phenomenon is a parable for modern medicine. It is likely that access to a new diagnostic technique, a powerful armoury of medical and surgical treatments and the necessity for doctors to feel they are doing something positive for the patient, have created an incorrect disease model for asymptomatic endometriosis. As responsible clinicians and medical scientists it behoves us to honestly re-examine our approach to this phenomenon.

Endometriosis↗
PubMed1996

Effect of gonadotrophin on cell and matrix retention and expression of metalloproteinases and their inhibitor in cultured human granulosa cells modelling corpus luteum function.

Granulosa cells were prepared from follicular aspirates obtained at oocyte collection for in-vitro fertilization (IVF) and maintained in culture. Substantial loss of cells from the culture surface occurred in the absence of gonadotrophin when cells were maintained on a thin layer of extracellular matrix (ECM) using a defined, serum-free medium. This cell loss was clearly and significantly reduced in the presence of human chorionic gonadotrophin (HCG) by days 4-6 of culture, and occurred in conjunction with loss of ECM. Analysis of culture medium by zymography using gelatin as substrate demonstrated the presence of metalloproteinases (MMP), MMP-9 (gelatinase B) appearing as the predominant band. Measurement of overall gelatinase activity in culture media revealed a progressive fall in gelatinase expressed on a per cell basis in media from HCG-treated cultures and this was less marked in controls. This suppression of gelatinase activity was consistent with an observed increase in production of tissue inhibitor of metalloproteinase-1 (TIMP-1) by HCG-treated cells, which was significant by days 6-8 of culture. We speculate that stabilization of the ECM may be an important aspect of HCG action in the corpus luteum.

Cells, Cultured↗